Cancers (Aug 2023)
Association of Hepatobiliary Phase of Gadoxetic-Acid-Enhanced MRI Imaging with Immune Microenvironment and Response to Atezolizumab Plus Bevacizumab Treatment
- Yosuke Tamura,
- Atsushi Ono,
- Hikaru Nakahara,
- Clair Nelson Hayes,
- Yasutoshi Fujii,
- Peiyi Zhang,
- Masami Yamauchi,
- Shinsuke Uchikawa,
- Yuji Teraoka,
- Takuro Uchida,
- Hatsue Fujino,
- Takashi Nakahara,
- Eisuke Murakami,
- Masataka Tsuge,
- Masahiro Serikawa,
- Daiki Miki,
- Tomokazu Kawaoka,
- Wataru Okamoto,
- Michio Imamura,
- Yuko Nakamura,
- Kazuo Awai,
- Tsuyoshi Kobayashi,
- Hideki Ohdan,
- Masashi Fujita,
- Hidewaki Nakagawa,
- Kazuaki Chayama,
- Hiroshi Aikata,
- Shiro Oka
Affiliations
- Yosuke Tamura
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Atsushi Ono
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Hikaru Nakahara
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Clair Nelson Hayes
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Yasutoshi Fujii
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Peiyi Zhang
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Masami Yamauchi
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Shinsuke Uchikawa
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Yuji Teraoka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Takuro Uchida
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Hatsue Fujino
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Takashi Nakahara
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Eisuke Murakami
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Masataka Tsuge
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Masahiro Serikawa
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Daiki Miki
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Tomokazu Kawaoka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Wataru Okamoto
- Cancer Treatment Center, Hiroshima University Hospital, Hiroshima 734-8551, Japan
- Michio Imamura
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Yuko Nakamura
- Department of Diagnostic Radiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Kazuo Awai
- Department of Diagnostic Radiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Masashi Fujita
- Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan
- Hidewaki Nakagawa
- Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan
- Kazuaki Chayama
- Collaborative Research Laboratory of Medical Innovation, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Hiroshi Aikata
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Shiro Oka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- DOI
- https://doi.org/10.3390/cancers15174234
- Journal volume & issue
-
Vol. 15,
no. 17
p. 4234
Abstract
It has been reported that high intensity in the hepatobiliary (HB) phase of Gd-EOB-DTPA-enhanced MRI (EOB-MRI) is associated with an immune-cold microenvironment in HCC. The aim of this study is to reveal whether non-high-intensity HCCs are homogeneous with respect to the immune microenvironment and to investigate the predictive ability of EOB-MRI for the response to atezolizumab + bevacizumab therapy (Atezo/Bev). The association between differences in stepwise signal intensity of HB phase and molecular subtypes and somatic mutations associated with the immune microenvironment was investigated in 65 HCC patients (cohort 1). The association between EOB-MRI and the therapeutic effect of Atezo/Bev was evaluated in the Atezo/Bev cohort (60 patients in cohort 2). The proportion of HCCs having CTNNB1 mutations and classified as Chiang CTNNB1 and Hoshida S3 was high in the high-intensity HB-phase group. Infiltration of tumor-associated macrophages (TAM) and regulatory T-lymphocytes (Treg) was characteristic of the high-intensity and low-intensity groups, respectively. Although EOB-MRI could not predict the response to Atezo/Bev treatment, our results demonstrate that EOB-MRI could serve as a surrogate marker predicting the immune microenvironment. This suggests that Atezo/Bev treatment can be selected regardless of signal intensity in the EOB-MRI HB phase.
Keywords
- hepatocellular carcinoma
- Gd-EOB-DTPA-enhanced MRI
- β-catenin mutation
- surrogate marker
- immune microenvironment
- atezolizumab plus bevacizumab therapy
